M. Amini et al. / Chinese Chemical Letters 25 (2014) 166–168
167
H
H
N
N
H
N
H
N
N
N
N
N
N
N
N
N
N
N
H
P
P
N
H
P
P
P
P
P
P
P
N
N
H
L3
L2
L1
Scheme 1. The phosphazane oligomers (L1–3) used as ligand in Suzuki reaction.
3. Results and discussion
select the best solvent from the commonly used ones. The
solvents, such as DMF, DMA, DMF/H2O (1/1, v/v), i-PrOH, dioxane
and toluene, gave low to good yields ranging from 20% to 85% as
illustrated in Table 1, (entries 7–12). However, when we used
water, a satisfactory result was obtained and H2O was found to
be the best choice in the presence of KOH as base catalyzed by
Pd(OAc)2/L1 at 90 8C for 2 h (entry 9). In the final step, we
examined the effects of bases. The activity towards cross-
coupled products was increased when KOH was replaced with
K2CO3, while other bases, such as NaOAc, Na2CO3 and K3PO4 gave
yields of 58%, 72% and 49%, respectively (entries 13–16).
Replacement of inorganic bases by the organic base, Et3N,
afforded low product yields (entry 17).
Phosphorus trichloride and PhNH2, react readily to form a
series of PhNH/PhN-substituted P(III) phosphazanes. According to
our previous literature [15,16], the nearly quantitative product L1
is obtained at 110 8C in toluene, with a PCl3:PhNH2 molar ratio of
1:4.8. Compound L2 is formed in greater than 80% yield by reaction
of PCl3 with PhNH2 (1:6 molar ratio, 2 h, 0 8C) in methylene
chloride. Also at r.t. with a PCl3:PhNH2 molar ratio of 1:5, the main
product L3 is produced. To investigate the reactivity of L1–3 as
ligand, we first employed 4-acetylbromobenzene and phenyl-
boronic acid as substrates to optimize the reaction conditions.
Their coupling reactions were carried out under a variety of
palladium sources, bases and solvents. The results are summa-
rized in Table 1.
The catalytic applicability of the phosphazane ligand L1 was
explored with a range of aryl halides and arylboronic acids with the
results summarized in Table 2. All the reactions were carried out at
90 8C in air using H2O as a reaction solvent.
In
a comparative study, we applied these ligands in
conjunction with Pd(OAc)2 as pre-catalyst for the Suzuki
coupling reaction of 4-acetylbromobenzene and phenylboronic
acid in DMF as solvent at 90 8C. Results (entries 1–3) show that all
three ligand L1–3 are very efficient and suitable ligands for the
Suzuki coupling reaction with Pd(II) as pre-catalyst. On the basis
of higher yields for L1 compared to others, L1 was selected as the
ligand of choice for this reaction. Then we carried out screening
of palladium salts for better performance of the reaction and
other palladium sources, including Pd(OAc)2, proved to be less
effective in the reaction of 4-MeCO-PhBr and phenylboronic acid
(entries 4–6). The next step was to optimize the conditions to
As shown in Table 2, the Suzuki coupling of various
phenylboronic acids with aryl iodide and bromide provided
good to excellent yields of the products (entries 1–16). The
reactions between aryl iodides and various phenylboronic acids
were quantitative and afforded biphenyl derivatives in 91%–97%
yields within 2 h with the use of 0.5 mol% of Pd(OAc)2 in H2O. It is
worth noting that the most electron-deficient aryl bromides, 4-
acetyl and 4-nitro bromobenzene, quantitatively gave the
coupling products (entries 12 and 16). In order to test the
feasibility of this protocol for challenging substrates, we also
conducted the Suzuki reactions with aryl chlorides and observed
moderate to good product yields (entries 17–21). High catalytic
activity was observed in the coupling of phenylboronic acid and
4-methoxyphenylboronic acid with aryl iodides and bromides,
and moderate to good activity with chlorides. 2-Methoxyphe-
nylboronic acid was less reactive in comparison to both
phenylboronic acid and 4-methoxy phenylboronic acid (entries
2, 10 and 22).
Recently, Iranpoor and co-workers reported the use of 1,3,2,4-
diazadiphosphetidine compounds (L1–3) as ligands for Pd(II)-
catalyzed Suzuki coupling reactions of aryl iodides, bromides, and
chlorides under base-free conditions in water [17]. In fact, they
used high amounts of phosphazen ligands (0.3 mmol) as both a
ligand and a base. According to high cost and toxicity of these
ligands, use of a high amount of them is not good idea and
therefore in this work we use only 1.0 mol% of phosphazane
derivatives as ligand (0.01 mmol) for Suzuki coupling reaction. In
contrast to similar, previously reported systems, the catalytic
system presented in this paper does not suffer from the harsh
reaction conditions, such as using large amounts of hazardous
phosphine-based ligands, long reaction time and high reaction
temperature, but both two systems are almost equally effective
Suzuki coupling catalysts.
Table 1
The optimized reaction condition for the Pd-catalyzed Suzuki reaction.a
Entry
Ligand
Base
Solvent
Pd source
Yield (%)b
1
2
L1
L2
L3
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
KOH
DMF
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
85
81
81
79
81
63
80
85
87
63
41
20
97
58
72
49
13
KOH
DMF
3
KOH
DMF
4
KOH
DMF
5
KOH
DMF
Pd(CH3CN)2Cl2
K2PdCl4
6
KOH
DMF
7
KOH
DMA
H2O/DMF
H2O
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
8
KOH
9
KOH
10
11
12
13
14
15
16
17
KOH
i-PrOH
Toluene
Dioxane
H2O
KOH
KOH
K2CO3
NaOAc
Na2CO3
K3PO4
Et3N
H2O
H2O
H2O
H2O
a
Reaction conditions: 1.0 mmol of 4-acetylbromobenzene, 1.2 mmol of phe-
nylboronic acid, 2 mmol of bases, 0.5 mol% Pd(OAc)2, 1.0 mol% ligand (L1–3), 90 8C,
3 mL solvent, 2 h.
b
Isolated yield.